Captain Marvan Atapattu (back) and left arm fast bowler Ruchira Perera (hamstring) have been ruled out of the series while the team management is assessing the fitness of two other key players.
Former skipper Sanath Jayasuriya (thigh) and left-arm seamer Chaminda Vaas (side strain) too are on the injured list after missing a preceding three-match one-day series that Sri Lanka lost 2-0.
"At the moment Sanath is ahead of Vaas in terms of recovery. We don't want to rush him to play unless he's 100 percent fit," coach Tom Moody told reporters.
Stand-in skipper Mahela Jayawardene felt the team could do well in the Tests despite failing in one-dayers.
"Even though we had a bad time in the one-dayers, our recent Test performances have not been that bad and overall we have performed really well in the last 12 months," Jayawardene said.
Injuries to several leading players forced Sri Lankan selectors to name an expanded squad of 18 but are expected to prune the squad down to 15 after fitness tests.
The injuries have also given the selectors an opportunity to try out some talented young players like Chamara Kapugedara (19) and Ian Daniel (24).
Kapugedara has already played in ten one-dayers but has yet to make his Test debut. Daniel, a technically solid batsman, is considered as the long-term replacement for Atapattu.
Pakistan skipper Inzamam-ul Haq felt the Tests would be challenging.
"The one-dayers are history and we have to start afresh. Although a few of Sri Lanka's top players are injured, they are a good a side at home and we need to work hard," Inzamam said.
Off-spinner Muttiah Muralitharan poses the biggest threat for Pakistan.
Muralitharan missed their Test series in 2004 due to an injury after grabbing eight wickets against Pakistan in the Asian Test Championship final in 2002.
Pakistan's coach Bob Woolmer conceded that Muralitharan, who recently passed 1,000 international wickets, could be a threat in the Tests.
"Obviously, he has got a great record over the years and will take wickets on any pitch," said Woolmer.
"We have worked a lot on how to play him and had success in the one-dayers against him. Hopefully, we can take that into the Test series as well," he said.
The second Test will be held in Kandy from April 3.
The teams (from):
Sri Lanka: Mahela Jayawardene (capt), Kumar Sangakkara, Sanath Jayasuriya, Upul Tharanga, Michael van Dort, Ian Daniel, Tillakaratne Dilshan, Thilan Samaraweera, Chamara Kapugedera, Chaminda Vaas, Farveez Maharoof, Lasith Malinga, Dammika Prasad, Nuwan Kulasekera, Dilhara Fernando, Muttiah Muralitharan, Malinga Bandara, Sajeewa Weerakoon.
Pakistan: Inzamam-ul-Haq (captain), Younis Khan, Mohammad Yousuf, Abdul Razzaq, Shahid Afridi, Shoaib Malik, Kamran Akmal, Salman Butt, Danish Kaneria, Rana Naved-ul-Hasan, Rao Iftikhar, Imran Farhat, Faisal Iqbal, Umar Gul, Mohammad Asif and Arshad Khan.
Umpires: Rudi Koertzen (RSA) Steve Davis (AUS), TV umpire: Tyronne Wijewardene (SRI)
Match Referee: Alan Hurst (AUS)